H Schutte, G Hermle, W Seeger and F Grimminger
Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.

Biophysical factors have been implicated in the development of pulmonary ischemia-reperfusion injury. In isolated rabbit lungs, the impact of vascular and alveolar distension, with and without alveolar oxygen supply, was investigated. With interruption of both perfusion (zero intravascular pressure) and ventilation, reperfusion after 120 min of warm ischemia resulted in transient pulmonary hypertension, with largely unchanged microvascular pressures, followed by a dramatic leakage response with approximately 10-fold increased capillary filtration coefficients (Kfc) and severe edema. Maintenance of vascular distension during ischemia (intravascular pressure of approximately 2 to 3 mm Hg) reduced the hypertension and fully suppressed the leakage. Employing ischemic periods of 180 and 240 min, ventilation of the lungs with 21 or 100% oxygen > ventilation with nitrogen during perfusion stop, but not static anoxic inflation, further enhanced the protective effect of vascular distension. At optimal biophysical support (vascular distension and ongoing normoxic ventilation), even 240 min of warm ischemia was tolerated with only moderate Kfc increase. We conclude that biophysical factors exert marked influence on pulmonary ischemia- reperfusion injury. Maintenance of vascular distension possesses strong protective potency, further enhanced by continued ventilation and alveolar oxygen supply during ischemia. These results may have important implications for organ preservation in lung transplantation.

This article has been cited by other articles:

				Y.-W. Chen, K. C. Hwang, C.-C. Yen, and Y.-L. Lai Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2004; 287(1): R21 - R26. [Abstract] [Full Text] [PDF]

				J. M. Dodd-o, L. E. Welsh, J. D. Salazar, P. L. Walinsky, E. A. Peck, J. G. Shake, D. J. Caparrelli, B. T. Bethea, S. M. Cattaneo, W. A. Baumgartner, et al. Effect of bronchial artery blood flow on cardiopulmonary bypass-induced lung injury Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H693 - H700. [Abstract] [Full Text] [PDF]

				J. M. Dodd-o, M. L. Hristopoulos, N. Faraday, and D. B. Pearse Effect of ischemia and reperfusion without airway occlusion on vascular barrier function in the in vivo mouse lung J Appl Physiol, November 1, 2003; 95(5): 1971 - 1978. [Abstract] [Full Text] [PDF]

				H. SCHUTTE, K. MAYER, H. BURGER, M. WITZENRATH, T. GESSLER, W. SEEGER, and F. GRIMMINGER Endogenous Nitric Oxide Synthesis and Vascular Leakage in Ischemic-Reperfused Rabbit Lungs Am. J. Respir. Crit. Care Med., August 1, 2001; 164(3): 412 - 418. [Abstract] [Full Text] [PDF]

				D. B. Pearse and P. M. Becker Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2077 - H2084. [Abstract] [Full Text] [PDF]

				H. Schutte, M. Witzenrath, K. Mayer, N. Weissmann, A. Schell, S. Rosseau, W. Seeger, and F. Grimminger The PDE inhibitor zaprinast enhances NO-mediated protection against vascular leakage in reperfused lungs Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L496 - L502. [Abstract] [Full Text] [PDF]

				G. HERMLE, H. SCHÜTTE, D. WALMRATH, K. GEIGER, W. SEEGER, and F. GRIMMINGER Ventilation-Perfusion Mismatch after Lung Ischemia-Reperfusion . Protective Effect of Nitric Oxide Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1179 - 1187. [Abstract] [Full Text]

				D. B. Pearse, E. M. Wagner, and S. Permutt Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs J Appl Physiol, January 1, 1999; 86(1): 123 - 132. [Abstract] [Full Text] [PDF]